Biochem - Metabolism (Sugar Metabolism & Disorders) Flashcards
Pg. 106-107 in First Aid 2014 Sections include: -Disorders of fructose metabolism -Disorders of galactose metabolism -Sorbitol -Lactase deficiency
Give 2 examples of disorders of fructose metabolism.
(1) Essential fructosuria (2) Fructose intolerance
What is the defect in Essential fructosuria?
Involves a defect in fructokinase
What is the mode of inheritance of essential fructosuria?
Autosomal recessive
What kind of condition (in terms of severity) is essential fructosuria, and why?
A benign, asymptomatic condition, since fructose is not trapped in cells
What are the symptoms of essential fructosuria?
Symptoms: Fructose appears in blood and urine
How do fructose metabolism disorders compare/contrast to disorders of galactose metabolism in terms of severity of symptoms?
Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.
What causes fructose intolerance?
Hereditary deficiency of aldolase B.
What is the mode of inheritance of fructose intolerance?
Autosomal recessive
What is the pathogenesis of fructose intolerance?
Hereditary deficiency of aldolase B… Fructose 1-P accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
In what setting do fructose intolerance symptoms present?
Symptoms present following consumption of fruit, juice, or honey
What will the urine dipstick results be in patients with fructose intolerance, and why? In general, what kind of sugar can be detected in the urine, and what is the clinical significance of this?
Urine dipstick will be negative (tests for glucose only); Reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism)
What are 4 symptoms associated with fructose intolerance?
Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
What is the treatment for fructose intolerance?
Treatment: Decrease intake of both fructose and sucrose (glucose + fructose)
Diagram the major steps of fructose metabolism in the liver, labeling the following key correlations: (1) Fructokinase deficiency = Essential fructosuria (2) Aldolase B deficiency = Fructose intolerance (3) Fructose bypasses rate-limiting step of glycolysis (PFK) via this pathway.
See p. 106 in First Aid 2014 for visual at bottom of page
What are 2 disorders of galactose metabolism?
(1) Galactokinase deficiency (2) Classic galactosemia
What is Galactokinase deficiency? What metabolic change occurs if galactose is present in the diet in a patient with this deficiency?
Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in diet.
What is the severity of galactokinase deficiency? What is its mode of inheritance?
Relatively mild condition. Autosomal recessive
What are symptoms associated with galactokinase deficiency?
Symptoms: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.
What causes classic galactosemia?
Absence of galactose-1-phosphate uridyltransferase.
What is the mode of inheritance of classic galactosemia?
Autosomal recessive
What causes damage in classic galactosemia?
Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye).
What are 5 symptoms associated with classic galactosemia?
Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
What is the treatment for classic galactosemia?
Treatment: exclude galactose and lactose (galactose + glucose) from diet
For enzymes associated with severe deficiencies: Fructose is to ____ as Galactose is to ____ .
Fructose is the Aldolase B as Galactose is to UridylTransferase; Think: “FAB GUT”
What metabolic change results from the more serious defects of galactose metabolism?
The more serious defects lead to (PO4)3- depletion
What condition can classic galactosemia cause in neonates?
Classic galactosemia can lead to E. coli sepsis in neonates
Diagram the major steps in galactose metabolism, including the activity of the following enzymes: (1) Aldose reductase (2) Galactokinase (3) Uridyltransferase. Also, label the link to glycolysis/gluconeogenesis.
See p. 107 in First Aid 2014 for visual near top left of page
What is the purpose of converting glucose to sorbitol? What enzyme does this?
An alternative method of trapping glucose in the cell (besides converting it to G-6-P through Hexokinase/Glucokinase) is to convert it to its alcohol counterpart, called sorbitol, via aldolase reductase
What is the role of sorbitol dehydrogenase?
(After aldolase reductease converts glucose to sorbitol) Some tissues then convert sorbitol to fructose using sorbitol dehydrogenase
What kind of damage can result from an insufficient amount of sorbitol dehydrogenase, and why? Give 3 examples of conditions that may result.
Tissues with an insufficient amount of this enzyme are at risk for intracellular sorbitol accumulation, causing osmotic damage (e.g., cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in patients)
What happens to galactose when it is at high bood levels? What enzyme catalyzes this?
High blood levels of galactose also result in conversion to the osmotically active galactitol via aldose reductase
Which 3 organs/body parts have both aldose reductase and sorbitol dehydrogenase enzymes?
(1) Liver, (2) Ovaries, and (3) Seminal vesicles have both enzymes.
What 3 organs/body parts have only aldose reductase? What is an additional organ/body part noted for having primarily adolase reductase?
(1) Schwann cells, (2) Retina, and (3) Kidneys have only aldose reductase; Lens has primarily aldose reductase.
Draw the reactions catalyzed by Aldose reductase and Sorbitol dehydrogenase in organs/body parts that have both enzymes.
See p. 107 in First Aid 2014 for visual near bottom-middle of page
Draw the reaction catalyzed by Aldose reductase in organs/body parts that have only or primarily this enzyme.
See p. 107 in First Aid 2014 for visual near bottom-middle of page
What is lactase deficiency? What is the normal function of lactase, and where does it function ?
Insufficient lactase enzyme => dietary lactose intolerance. Lactase functions on the brush border to digest lactose (in human and cow milk) into glucose and galactose
What defines primary lactase deficiency? In what patient populations is it common?
Primary: age-dependent decline after childhood (absence of lactase-persistent allele), common in people of Asian, African, or Native American descent
What defines secondary lactase deficiency?
Secondary: loss of brush border due to gastroenteritis (e.g., rotavirus), autoimmune disease, etc.
What defines congenital lactase deficiency?
Congenital lactase deficiency: rare, due to defective gene
What stool and breath findings occur with lactose intolerance test in a lactase deficient patient?
Stool demonstrates low pH and breath shows high hydrogen count with lactose intolerance test
What describes the intestinal biopsy in patients with hereditary lactose intolerance?
Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance
What are 4 symptoms/findings associated with lactase deficiency?
Bloating, cramps, flatulence, osmotic diarrhea
What is the treatment for lactase deficiency?
Avoid dairy products or add lactase pills to diet; Lactose-free milk
